Compositions and methods for treating and preventing urolithiasis and conditions associated therewith

Abstract

Compositions and methods for the treatment of urinary calculi and fragments thereof are provided. Compositions and methods for the prevention and/or treatment of renal and urinary colic caused by urinary calculi or fragments are also provided. Such compositions and methods provide locally effective amounts of diazepam sufficient to prevent formation of and/or expel ureteral calculi and fragments thereof and thus prevent and/or treat pain associated with calculi and fragments thereof.

The invention claimed is: 
     
       1. A method for treatment of kidney stones, ureteral stones and acute ureteral colic or renal colic in a mammal, said method comprising:
 administering into the bladder or ureter a locally effective amount of diazepam of said mammal for whom such treatment is needed or desirable. 
 
     
     
       2. The method of  claim 1 , wherein the mammal is a human. 
     
     
       3. The method of  claim 1 , wherein the effective amount of diazepam is administered by intraurethral injection or by instillation through a bladder catheter. 
     
     
       4. The method of  claim 1 , wherein the effective amount of diazepam promotes expulsion of ureteral stones. 
     
     
       5. The method of  claim 1 , wherein the effective amount of diazepam promotes expulsion of ureteral stone fragments. 
     
     
       6. The method of  claim 1 , wherein the effective amount of diazepam is less than 50 mg. 
     
     
       7. The method of  claim 6 , wherein the effective amount of diazepam comprises from about 1 mg to about 30 mg. 
     
     
       8. The method of  claim 7 , wherein the effective amount of diazepam comprises from about 5 mg to about 20 mg. 
     
     
       9. The method of  claim 6 , wherein the effective amount of diazepam comprises less than about 5 mg. 
     
     
       10. The method of  claim 1 , wherein following said administration combined plasma level of diazepam and desmethyldiazepam does not exceed about 100 ng/ml. 
     
     
       11. The method of  claim 10  wherein following said administration the combined plasma level of diazepam and desmethyldiazepam does not exceed about 50 ng/ml. 
     
     
       12. The method of  claim 11 , wherein following said administration the combined plasma level of diazepam and desmethyldiazepam does not exceed about 25 ng/ml. 
     
     
       13. The method of  claim 1 , wherein the diazepam is administered as an adjuvant to extracorporeal shock wave lithotripsy (ESWL). 
     
     
       14. A pharmaceutical composition for the treatment of kidney stones, ureteral stones and colic associated therewith in a mammal comprising:
 diazepam and pharmaceutically acceptable excipients, wherein such dosage form is suitable for local administration into the bladder or ureter of said mammal in a locally effective amount to treat kidney stones, ureteral stones and colic associated therewith in said mammal. 
 
     
     
       15. The pharmaceutical composition of  claim 14  in a form selected from the group consisting of suppositories, ointments, solutions, gels, sprays, creams, suspensions, liquids, powders and pastes and any combination thereof. 
     
     
       16. The pharmaceutical composition of  claim 15  in the form of a gel. 
     
     
       17. The pharmaceutical composition of  claim 16 , wherein the gel is a matrix-based gel.